Oxidized cellulose is produced by the oxidation of cellulose, for example with dinitrogen tetroxide. This process converts primary alcohol groups on the saccharide residues to carboxylic acid group, forming uronic acid residues within the cellulose chain. The oxidation does not proceed with complete selectivity, and as a result hydroxyl groups on carbons 2 and 3 are occasionally converted to the keto form. These ketone units introduce an alkali labile link, which at pH 7 or higher initiates the decomposition of the polymer via formation of a lactone and sugar ring cleavage. As a result, oxidized cellulose is biodegradable and bioabsorbable under physiological conditions.
The preferred oxidized cellulose for practical applications is oxidized regenerated cellulose (ORC) prepared by oxidation of a regenerated cellulose, such as rayon. It has been known for some time that ORC has haemostatic properties. ORC has been available as a haemostatic product called SURGICEL (Registered Trade Mark of Johnson & Johnson Corporation) since 1950. This product is produced by the oxidation of a knitted rayon material.
A modification of porosity, density and knit pattern led to the launch of a second ORC fabric product, INTERCEED (Registered Trade Mark-Johnson & Johnson Corporation) which was shown to reduce the extend of post-surgical adhesions in abdominal surgery.
U.S. Pat. No. 2,517,772 (Doub et al.) describes improved haemostatic materials obtained by impregnating ORC fabric with thrombin.
EP-A-0437095 describes a neutralised ORC material prepared by contacting an as-synthesised acidic ORC material with a solution of a basic salt of a weak organic acid, such as sodium acetate. The resulting neutralised product is indicated for haemostasis and adhesion prevention.
EP-A-0562862 describes bioabsorbable sponge materials for use as wound implants. The materials comprise a collagen sponge matrix having an oriented substructure therein. The matrix and/or substructures may comprise oxidized regenerated cellulose. There is no disclosure of the use of such materials for the treatment of chronic wounds.
WO98/00180 describes the use of freeze-dried sponges of collagen admixed with oxidized regenerated cellulose (ORC) for the treatment of chronic wounds. EP-A-1153622 further describes sterile sponge pads of this type based on bovine collagen/ORC mixtures that exhibit high reproducibility and tensile strength both when wet and when dry. The sponge pad described in EP-A-1153622 is freeze-dried and at least 80% by weight of the sponge consists of a mixture of bovine collagen and oxidized regenerated cellulose in the weight ratio 60:40 to 40:60.
Sponges of bovine collagen mixed with ORC made in accordance with EP-A-1153622 are commercially available from Ethicon, Inc. under the Registered Trade Mark PROMOGRAN. These products have been highly successful, especially for the treatment of chronic wounds. The materials are of natural, biological origin (albeit chemically modified), and consequently tend to have low antigenicity. The materials are generally bioabsorbable, which reduces the trauma associated with removal of conventional wound dressing materials from the surface of the wound. Furthermore, some of these materials can have positive therapeutic effects on wound healing.
It is an object of the present invention to provide improved wound dressing materials for mammalian wounds, and especially for human, chronic wounds, such as venous ulcers, decubitis ulcers and diabetic ulcers. Such chronic wounds generally exhibit little or no bleeding or adhesion to other body tissues.